Galvus (vildagliptin), seeking to become a new once-daily oral treatment option for type 2 diabetes, has demonstrated impressive efficacy, especially in patients with poor glycemic control, as well as weight loss benefits in obese patients.

These new findings from phase III studies were presented at a late-breaker session at the 66th Scientific Sessions of the American Diabetes Association (ADA) meeting in Washington, DC.

The combination of Galvus, a member of the DPP-4 inhibitor class, and pioglitazone led to an overall 1.9 per cent reduction in HbA1c (a measure of blood sugar control also known as A1c). Pioglitazone is an insulin sensitizer known as a thiazolidinedione, or TZD. Two-thirds of people (65 per cent) on Galvus and pioglitazone achieved the ADA-defined A1c goal of less than or equal to 7 per cent versus 42 per cent of those who achieved this goal on monotherapy (Galvus 42.5 per cent, pioglitazone 42.9 per cent).

More importantly, a reduction of up to 2.8 per cent in A1c was seen among patients with poor glycemic control who had the highest mean baseline blood sugar levels (about 10 per cent) as measured by A1c.

Also in this study, patients over age 65 who were given Galvus and pioglitazone showed an A1c drop of 2.3 per cent from a mean A1c baseline of 8.4 per cent. In obese patients, with a Body Mass Index (BMI) equal to or over 35, patients given Galvus and pioglitazone showed a decline of 2.2 per cent from a mean A1c baseline of 8.6 per cent.

In a separate head-to-head comparison with rosiglitazone, another insulin sensitizer, Galvus demonstrated comparable efficacy. Among severely obese Galvus-treated patients, there was a mean reduction of body weight greater than 1 kg, with an overall mean difference of 2.8 kg between the Galvus and rosiglitazone treatment groups.

"These new data underscore the significant efficacy and good tolerability that have been consistently observed in the robust Galvus clinical development program," said James Shannon, MD, Head of Development at Novartis Pharma AG.

"The magnitude of A1c reductions seen in the combination of Galvus and a TZD is encouraging for patients struggling to reach and maintain their blood sugar levels. The trial results for Galvus continue to reinforce the benefits of treating both islet dysfunction and insulin resistance in type 2 diabetes," Shannon said.

Throughout the Phase III program, Galvus has shown clinically significant and consistent A1c reductions both as monotherapy and in combination with other oral and injectable anti-diabetic agents. Galvus has demonstrated a good tolerability profile in these studies, with no weight gain overall and an incidence of hypoglycemia (excessively low blood sugar) and edema (fluid retention) similar to placebo in monotherapy trials.

"As the diabetes epidemic continues to grow worldwide, there is a very real and urgent need for new ways to help control blood sugar levels in people with type 2 diabetes," said Julio Rosenstock, MD, Director of Dallas Diabetes and Endocrine Center at Medical City, Clinical Professor of Medicine, University of Texas, Southwestern Medical School Dallas, Texas and a lead investigator in the Galvus/pioglitazone trial. "We were pleased to see the especially steep reductions of glucose in the subanalysis of patients with the highest blood sugar levels. However, this high baseline population represents a difficult to treat group and these patients usually require a multi-drug strategy to reach glycemic goal."

Galvus was accepted for US regulatory review earlier in 2006. The submission includes data from clinical trials involving more than 4,300 patients worldwide. Regulatory filings in the EU are planned to be completed later in 2006.

The two trials were highlighted at the ADA late-breaker session as part of a broad overview of clinical data summarizing the development as well as overall efficacy and tolerability of Galvus.

The first was a six-month clinical trial evaluating the combination of Galvus and pioglitazone (Pio) in patients with type 2 diabetes. The study evaluated 592 patients who had never been previously treated for type 2 diabetes and who had a baseline A1c of between 7.5% and 11%. It involved four treatment groups: (1) Galvus 100 mg; (2) Pio 30 mg; (3) Galvus 100 mg + Pio 30 mg; (4) Galvus 50 mg + Pio 15 mg.

Among patients with baseline A1c of 9% or greater, the combination of Galvus and Pio produced a 2.8% reduction in A1c. In the overall population, patients receiving Galvus 100 mg + Pio 30 mg saw a statistically significant overall reduction in A1c compared to those on Pio alone (1.9% vs. 1.4%, p < 0.001).

Adverse events were consistent with the individual safety profiles of Galvus and TZDs. The patients treated with the combination of Galvus and Pio experienced no significant additional weight gain and less edema (fluid retention) compared to patients taking Pio alone.

The second trial involved 700 patients in a six-month head-to-head comparison of Galvus (100 mg daily) and rosiglitazone (8 mg once/day). Galvus reduced blood sugar levels significantly (-1.1%) as measured by A1c, with no difference between treatment groups. Galvus treatment was not associated with weight gain overall, while people in the rosiglitazone group gained on average 1.6 kg. Galvus-treated patients also experienced a lower incidence of edema (2.5% vs. 4.9%).

The initial results from this trial were presented at an ADA poster session at 10:00 am EDT on Saturday, June 10 (abstract 557-P).

In an additional subgroup analysis of severely obese patients presented at the late-breaker session, there was a mean reduction of body weight greater than 1 kg in the Galvus group, with a mean difference between the Galvus and rosiglitazone groups of 2.8 kg.